TheraSphere for the Treatment of Liver Metastases

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00511862
• Collaborator: BTG International Inc. (Other)
• Enrollment: 151
• Locations: 5
• Arm: 1
• Duration (Months): 49.9
• Patients Per Site: 30.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study will evaluate Liver Progression Free Survival (PFS) and safety of TheraSphere treatment at doses of 120 Gy +/1 10% in patients at least 18 years of age diagnosed with metastatic disease to the liver that cannot be treated or is progressing following treatment with systemic or other liver-directed therapies.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Carcinoma, Neuroendocrine; Neoplasm Metastasis	Device: Yttrium 90 glass microspheres	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TheraSphere for the Treatment of Liver Metastases: An Open Label Trial of TheraSphere in Patients With Liver Metastases From Primary Colorectal Cancer, Neuroendocrine Cancer or Non-colorectal/Non-neuroendocrine Cancer
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TheraSphere Single arm, TheraSphere Yttrium 90 glass microspheres at 120 Gy +/- 10%; stratified by type of disease (colorectal cancer, neuroendocrine cancer, non-colorectal/non-neuroendocrine cancer	Device: Yttrium 90 glass microspheres; 120 Gy unilobar or bilobar infusion with the second infusion occurring 3-7 weeks following treatment of the first lobe; Other Names: TheraSphere

Outcome Measures

Primary Outcome Measures

1. Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) [From the date of first treatment until date of first documented progression; median patient follow-up 30 months]

   Progression per RECIST v 1.0 is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. A maximum of 5 target lesions per organ are assessed. To assess the impact of a non-systemic local therapy on progression, for the purposes of this trial, hepatic progression was defined as at least a 20% increase in the sum of the longest diameter of target hepatic lesions. Hepatic progression-free survival is the time from the day of first treatment with TheraSphere to determination of hepatic progression.

Secondary Outcome Measures

1. Overall Survival [Time from first TheraSphere treatment to death; median follow up 30 months]

   Duration of survival from date of first TheraSphere treatment to date of death or censored to last known date alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• diagnosis of metastatic disease to the liver that is refractory to, or inappropriate for, other systemic or liver-directed therapies

• unresectable liver metastases

• target tumors measurable using standard imaging techniques

• tumor replacement < or = 50% of total liver volume (visual estimation by investigator)

• Hypervascular tumors (visual estimation by investigator)

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

• minimum one month since most recent prior cancer therapy with the exception of patients receiving Sandostatin for neuroendocrine cancer

• patient informed consent

Exclusion Criteria:

• At risk of hepatic or renal failure within 21 days of treatment (serum creatinine > 2.0 mg/dL unless on dialysis; serum bilirubin ≥ 2.0 mg/dL; albumin < 2.0 mg/dL or any history of hepatic encephalopathy)

• contraindications to angiography and selective visceral catheterization including any non-correctable bleeding diathesis or coagulopathy, severe peripheral vascular disease or history of non-management allergy or intolerance to contrast, narcotics, sedatives or atropine

• severe liver dysfunction or presentation of pulmonary insufficiency or clinically evident history of chronic obstructive pulmonary disease

• cirrhosis or portal hypertension

• prior external beam radiation treatment to the liver

• prior TheraSphere treatment to the liver

• any intervention for, or compromise of the Ampulla of Vater

• clinically evident ascites (trace ascites on imaging is acceptable)

• any continuing complications of prior cancer therapy that have not improved or resolved prior to 21 days before first TheraSphere treatment

• significant life-threatening extrahepatic disease in judgment of physician

• concurrent enrollment in another study

• alternative available therapies in judgement of physician

• evidence on technetium-99m macroaggregated albumin scan that shows lung shunting > 30 Gy cumulative limit

• evidence on technetium-99m macroaggregated albumin scan showing potential for deposition of microspheres to the gastrointestinal tract that cannot be eliminated by catheter placement or corrective action using standard angiographic techniques

• positive serum pregnancy test in women of childbearing potential

• co-morbid disease or condition that puts the patient at undue risk or precludes use of TheraSphere in judgment of physician

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital, Robert H Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611-2927
2	John Hopkins Hospital	Baltimore	Maryland	United States	21287-4010
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Albany Medical Center	Albany	New York	United States	12208
5	Medical College of Wisconsin, Froedtert Hospital	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Boston Scientific Corporation
• BTG International Inc.

Investigators

• Principal Investigator: Al Benson III, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT00511862
• Other Study ID Numbers: G040148
• First Posted: Aug 6, 2007
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Boston Scientific Corporation: TheraSphere; radioactive microspheres; Yttrium-90; Yttrium glass microspheres
• Additional relevant MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis; Carcinoma, Neuroendocrine

Study Results

Participant Flow

Recruitment Details	151 patients recruited from January 19, 2007 to October 7, 2009
Pre-assignment Detail	Patients were assigned to groups on the basis of type of primary cancer - colorectal cancer; neuroendocrine cancer or non-colorectal/non-neuroendocrine. Subjects who unable to receive TheraSphere (target dose 120 Gy) due to vascular shunting to the lungs or GI tract were not enrolled in the study and did not receive yttrium 90 glass microspheres.

Arm/Group Title	Colorectal Cancer	Neuroendocrine Cancer	Non-Colorectal/Non-neuroendocrine
Arm/Group Description	Colorectal cancer patients with liver metastatic disease, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	Neuroendocrine cancer patients with liver metastatic disease, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	Patients with liver metastatic disease not arising from colorectal cancer or neuroendocrine cancer, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0
Period Title: Overall Study
STARTED	61	43	47
COMPLETED	61	43	47
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Colorectal Cancer	Neuroendocrine Cancer	Non-Colorectal/Non-neuroendocrine	Total
Arm/Group Description	colorectal cancer patients with liver metastatic disease, refractory to standard of care therapy	neuroendocrine cancer patients with liver metastatic disease, refractory to standard of care therapy	patients with liver metastatic disease not arising from colorectal cancer or neuroendocrine cancer, refractory to standard of care therapy	Total of all reporting groups
Overall Participants	61	43	47	151
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	29 47.5%	22 51.2%	20 42.6%	71 47%
>=65 years	32 52.5%	21 48.8%	27 57.4%	80 53%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (10.92)	61.8 (13.71)	66.1 (8.52)	63.7 (11.21)
Sex: Female, Male (Count of Participants)
Female	25 41%	19 44.2%	23 48.9%	67 44.4%
Male	36 59%	24 55.8%	24 51.1%	84 55.6%
Region of Enrollment (participants) [Number]
United States	61 100%	43 100%	47 100%	151 100%

Outcome Measures

1. Primary Outcome

Title	Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST)
Description	Progression per RECIST v 1.0 is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. A maximum of 5 target lesions per organ are assessed. To assess the impact of a non-systemic local therapy on progression, for the purposes of this trial, hepatic progression was defined as at least a 20% increase in the sum of the longest diameter of target hepatic lesions. Hepatic progression-free survival is the time from the day of first treatment with TheraSphere to determination of hepatic progression.
Time Frame	From the date of first treatment until date of first documented progression; median patient follow-up 30 months

Outcome Measure Data

Analysis Population Description

Patients receiving at least one TheraSphere treatment with images evaluable by RECIST

Arm/Group Title	Colorectal Cancer	Neuroendocrine Cancer	Non-Colorectal/Non-neuroendocrine	All Patients
Arm/Group Description	Colorectal cancer patients with liver metastatic disease, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	Neuroendocrine cancer patients with liver metastatic disease, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	Patients with liver metastatic disease not arising from colorectal cancer or neuroendocrine cancer, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	All patients in colorectal cancer, neuroendocrine cancer and non-colorectal/non-neuroendocrine groups
Measure Participants	58	43	46	147
Median (95% Confidence Interval) [Months]	3.0	17.9	2.9	3.4

2. Secondary Outcome

Title	Overall Survival
Description	Duration of survival from date of first TheraSphere treatment to date of death or censored to last known date alive.
Time Frame	Time from first TheraSphere treatment to death; median follow up 30 months

Outcome Measure Data

Analysis Population Description

In the neuroendocrine group, a median overall survival was not achieved so a post-hoc analysis of 2 year survival was performed in Outcome Measure 3.

Arm/Group Title	Colorectal Cancer	Non Colorectal/Non-Neuroendocrine	All Patients
Arm/Group Description	Colorectal cancer patients with liver metastatic disease, refractory to standard of care therapy who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	Patients with metastatic liver disease arising from primary cancers other than colorectal or neuroendocrine cancer who received intrahepatic TheraSphere yttrium-90 glass microspheres (target dose 120 Gy) on Day 0	All patients in colorectal cancer, neuroendocrine cancer and non-colorectal/non-neuroendocrine groups
Measure Participants	61	47	151
Median (95% Confidence Interval) [Months]	8.8	10.4	13.6

3. Post-Hoc Outcome

Title	2 Year Survival
Description	The percentage of patients in the neuroendocrine group alive at 2 years
Time Frame	24 months from treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neuroendocrine Cancer
Arm/Group Description	neuroendocrine cancer patients with liver metastatic disease, refractory to standard of care therapy
Measure Participants	43
Number [percentage of treated subjects]	79.1

Adverse Events

Time Frame	All adverse events collected for 3 months, device-related adverse events captured to month 18
Arm/Group Title	TheraSphere
Arm/Group Description	total population receiving at least one TheraSphere treatment
All Cause Mortality
	TheraSphere
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TheraSphere
	Affected / at Risk (%)	# Events
Total	21/151 (13.9%)
Blood and lymphatic system disorders
Decreased platelets	1/151 (0.7%)	1
GI hemorrhage	1/151 (0.7%)	1
Gastrointestinal disorders
Dehydration	1/151 (0.7%)	1
Esophagial varices	1/151 (0.7%)	1
GI ulcer	2/151 (1.3%)	2
Nausea	2/151 (1.3%)	2
Obstruction	2/151 (1.3%)	2
General disorders
Death	2/151 (1.3%)	2
Hepatobiliary disorders
Liver dysfunction/failure	2/151 (1.3%)	2
Infections and infestations
Infection	1/151 (0.7%)	1
Injury, poisoning and procedural complications
Vessel injury - lower extremity artery	1/151 (0.7%)	1
Metabolism and nutrition disorders
Hyperbilirubinemia	1/151 (0.7%)	1
Nervous system disorders
Abdominal or epigastric pain	5/151 (3.3%)	5
Renal and urinary disorders
Renal failure	1/151 (0.7%)	1
Vascular disorders
Thrombosis/embolus	1/151 (0.7%)	1
Other (Not Including Serious) Adverse Events
	TheraSphere
	Affected / at Risk (%)	# Events
Total	139/151 (92.1%)
Blood and lymphatic system disorders
Lymphopenia	16/151 (10.6%)	16
Gastrointestinal disorders
Constipation	11/151 (7.3%)	11
Nausea	59/151 (39.1%)	59
Vomitting	19/151 (12.6%)	19
General disorders
Fatigue	91/151 (60.3%)	91
Weight loss	11/151 (7.3%)	11
Metabolism and nutrition disorders
ALT > ULN	26/151 (17.2%)	26
AST >ULN	36/151 (23.8%)	36
Alkaline phosphatase >ULN	56/151 (37.1%)	56
Anorexia	36/151 (23.8%)	36
Bilirubin >ULN	19/151 (12.6%)	19
Hypoalbuminemia < LLN	19/151 (12.6%)	19
Nervous system disorders
Pain	62/151 (41.1%)	62

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.